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Pharmacology II > Anti-diabetic Medications (Exam 1) > Flashcards

Anti-diabetic Medications (Exam 1) Flashcards

1
Q

MOA of sulfonylureas

A

increase peripheral glucose utilization
decrease hepatic gluconeogenesis
increase number and sensitivity of insulin receptors

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2
Q

sulfonylureas are associated with

A

weight gain

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3
Q

functions of amylin

A

suppresses appetite
inhibits glucagon release
slows gastric emptying

which decreases plasma glucose

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4
Q

2nd gen sulfonylureas should be used with caution in patients with

A

cardiovascular disease
elderly patients

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5
Q

glyburide

A

hepatic metabolism into products with very low hypoglycemic activity
re-titration required when switching from glyburide to other sulfonylureas

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6
Q

glyburide use is restricted for

A

hepatic impairment and renal insufficiency patients

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7
Q

glipizide

A

shortest half life (2-4 hrs)
MDD cannot exceed 40 mg
90% glipizide metabolized in liver, rest excreted unchanged in urine

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8
Q

Glucotrol XL

A

24 hour action ER glipizide

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9
Q

when should glipizide be ingested?

A

30 minutes before breakfast to minimize postprandial hyperglycemia

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10
Q

glipizide is contraindicated in patients with

A

significant hepatic impairment

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11
Q

glipizide is preferred over glyburide in ____________ due to its

A

elderly and renal impaired patients

lower potency and shorter duration of action

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12
Q

glimepiride

A

once daily use alone or combined with insulin
half life: 5-9 hours
completely metabolized by liver

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13
Q

glimepiride achieves ____________________________ of any sulfonylurea compound

A

blood glucose lowering with the lowest dosage

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14
Q

Repaglinide

A

non-sulfonylurea insulin secretagogue with hypoglycemic activity
dosed alone or with metformin

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15
Q

repaglinide can be given to individuals with _____________ allergy because it has no __________________

A

sulfur or sulfonylurea

sulfur in its structure

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16
Q

MOA of repaglinide

A

acts on beta cells to release insulin by regulating K efflux through K channels

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17
Q

how is repaglinide similar to sulfonylureas

A

two common binding sites, one unique binding sites

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18
Q

Repaglinide is cleared by ___________ with a plasma half life of _____________

A

hepatic CYP3A4

1 hour

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19
Q

what metabolized repaglinide?

where are the metabolites excreted?

A

CYP3A4 and CYP2C8

the bile

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20
Q

repaglinide is indicated for use in

A

controlling postprandial glucose excursions

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21
Q

when on repaglinide, if a meal is delayed/skipped or contains low carbs,

A

hypoglycemia could be at risk

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22
Q

drugs usable in renally impaired and elderly

A

repgalinide
nateglinide
glipizide

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23
Q

nateglinide MOA

A

stimulates rapid and transient release of insulin from B cells through closure of ATP sensitive K channel

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24
Q

Nateglinide works better when

A

combined with non-secretagogue oral agents (metformin)

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25
Q

Nateglinide is metabolized in the liver by

A

CYP2C9 and CYP3A4

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26
Q

main adverse effect of nateglinide

A

hypoglycemia

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27
Q

when is nateglinide taken?

A

before a meal and reduces the postprandial rise in blood glucose levels

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28
Q

when is nateglinide absorbed?

peak concentration?

duration of action?

half life?

A

20 minutes after oral administration

less than 1 hour

4 hours

1 hour

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29
Q

metformin MOA

A

inhibits mitochondrial chain complex 1 which decreases ATP levels and activates AMPK
inhibits hepatic gluconeogenesis and opposes the action of glucagon

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30
Q

how does metformin use lead to increase in lactic acid?

A

it inhibits glycerol 3 phosphate dehydrogenase which stimulates conversion of pyruvate to lactate

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31
Q

what transcription factors does metformin activate using AMPK pathway

what happens when these factors are activated?

A

CBP (CREB-binding protein)
CRTC2 (CREB-regulated transcription coactivator 2)

decreased gluconeogenic gene expression

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32
Q

what is first line of therapy for T2DM?

A

metformin

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33
Q

metabolism of metformin

A

half life - 1.5-3hrs
not bound to plasma proteins
excreted by the kidneys as the active compound

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34
Q

metformin blocks ____________ and impairs the hepatic _________________

A

gluconeogenesis

lactic acid metabolism

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35
Q

in renal insufficiency, the biguanide _____________ and thereby increases the risk of _______________

A

accumulates

lactic acidosis

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36
Q

metformin is contraindicated if the

A

eGFR is less than 30ml/min

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37
Q

Metformin does not increase _____________ or provoke _______________

A

body weight

hypoglycemia

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38
Q

metformin can be used in combination with

A

insulin secretagogues or thiazolidinediones

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39
Q

metformin decreases the risk of

A

macrovascular and microvascular disease

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40
Q

which group of people does metformin prevent new onset T2DM in?

A

middle aged obese persons with impaired glucose tolerance and fasting hyperglycemia

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41
Q

toxic effects of metformin

A

GI upsets
diarrhea

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42
Q

how does metformin cause vitamin B12 deficiency?

A

it interferes with calcium dependent absorption of vitamin B 12 intrinsic factor complex

after many years of use

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43
Q

Metaglip

A

metformin and glipizide

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44
Q

Kombiglyze

A

saxagliptin and metformin

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45
Q

avandaryl

A

rosiglitazone and glimepiride

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46
Q

actoplus met

A

pioglitazone and metformin

47
Q

glucovance

A

metformin and glyburide

48
Q

avandamet

A

rosiglitazone and metformin

49
Q

duetact

A

pioglitazone and glimepiride

50
Q

janumet

A

sitagliptin and metformin

51
Q

prandimet

A

repaglinide and metformin

52
Q

jentadueto

A

metformin and linagliptin

53
Q

synjardy

A

empagliflozin and metformin

54
Q

xigduo

A

dapagliflozin and metformin

55
Q

ivonkamet

A

canagliflozin and metformin

56
Q

3 isoforms of intracellular nuclear transcription factors of thiazolidinediones

A

alpha (PPARa)
gamma (PPARy)
beta/delta (PPARb/d)

57
Q

PPARy is expressed on

A

liver, adipose tissue and muscle

58
Q

by activating PPARy, TZDs promote

A

fatty acid uptake and storage in adipose tissue rather than skeletal muscle and liver

59
Q

when PPAR alpha is activated

A

reduction in TG level
involved in regulation of energy homeostasis

60
Q

when PPAR gamma is activated

A

insulin sensitization
enhances glucose metabolism

61
Q

when PPAR b/d is activated

A

enhances fatty acid metabolism

62
Q

humoral stimulants of insulin release

A

glucose
mannose
leucine
arginine
AA
fatty acids

63
Q

hormonal stimulants of insulin release

A

glucagon
GLP-1
glucose dependent insulinotropic polypeptide
cholecystokinin
gastrin

64
Q

neural stimulants of insulin release

A

beta adrenergic stimulation
vagal stimulation

65
Q

drug stimulants of insulin release

A

sulfonylureas
meglinitide
nateglinide
isoproterenol
acetylcholine

66
Q

hormonal inhibitors of insulin release

A

somatostatin
insulin
leptin

67
Q

neural inhibitors of insulin release

A

alpha sympathomimetic effect of catecholamines

68
Q

drug inhibitors of insulin release

A

diazoxide
phenytoin
vinblastine
colchicine

69
Q

what lab values should you monitor while a patient is on metformin?

A

A1C
eGFR

70
Q

thiazolidinediones effects

A

increase insulin sensitivity
decrease insulin resistance
increase glucose utilization

71
Q

pioglitazone has more significant ___________ compared to rosiglitazone

A

lipid-lowering

72
Q

mechanism contributing to hypoglycemic effects of thiazolidinediones

A

increased expression of the glucose transporter GLUT4
increases ability to uptake glucose when stimulated by insulin

73
Q

Pioglitazone

A

PPARa and PPARy activity
absorbed in 2 hours
MDD 45mg
food delays uptake

74
Q

Pioglitazone is metabolized by

A

CYP2C8 and CYP3A4

75
Q

rosiglitazone

A

rapidly absorbed and highly protein bound
once or twice a day
metabolized by CYP2C8 and CYP2C9

76
Q

rosiglitazone is known to increase ________________ and has no effect on

A

HDL, LDL, total cholesterol

triglycerides

77
Q

alpha glucosidase inhibitors MOA

A

competitively inhibit the intestinal membrane bound alpha glucosidase enzymes

78
Q

alpha glucosidase inhibits effects

A

reduce post meal glucose excursions
delay digestion and absorption of starch and dissacharides

79
Q

alpha glucosidase inhibitors metabolism

A

NONE!

Digital is eliminated renally unchanged

80
Q

alpha glucosidase inhibitors are contraindicated in

A

people with IBD

81
Q

adverse effects of alpha glucosidase inhibitors

A

GI disturbance
excess undigested carbs –> increased bacterial digestion of polysaccharides

82
Q

exenatide

A

derivative of extendin-4 peptide in Gila monster venom
53% homology with native GLP1
glycine substitution to reduce degradation by DPP4

83
Q

liraglutide

A

soluble fatty acid-acylated GLP1 analog
half life - 12 hours

84
Q

dulaglutide

A

two GLP-1 analog molecules covalently linked to Fc fragment of human IgG4
protects the GLP1 moiety from inactivation by DPP4
HL - 5 days

85
Q

albiglutide

A

human GLP-1 dimer fused to human albumin
half life - 5 days

86
Q

adverse effect of GLP1 agonists

A

increase the risk of pancreatitis

87
Q

GLP1 effects

A

induces B cell growth
stimulates insulin production
reduces appetite

88
Q

DPP-4 enzyme

A

acts on incretin hormones (mainly GLP1 and GIP)
increase insulin secretion and decrease glucagon secretion

89
Q

half life of GLP1

A

less than 2 minutes

90
Q

half life of GIP

A

7 minutes in healthy people
5 minutes in people with type 2 diabetes

91
Q

DPP-4 inhibitors mechanism results in

A

increase circulating GLP-1
increase insulin levels
decrease glucagon levels

92
Q

metabolism of sitagliptin and linagliptin

A

excreted unchanged in urine

93
Q

metabolism of saxagliptin

A

metabolized by CYP3A4/5

major metabolite is a DPP4 inhibitor

94
Q

adverse effects of DPP4 inhibitors

A

GI disturbance

95
Q

SGLT2 accounts for __________ of glucose reabsorption

A

90%

96
Q

inhibition of SGLT2 causes

A

loss of glucose (glycosuria) and loss of water (osmotic diuresis)
no reabsorption of glucose

97
Q

how many GLUT transporters are there?

A

there is now 5!

GLUT5 helps absorb fructose from gut and kidney

98
Q

what so SGLTs do?

A

freely filter glucose by the renal glomeruli and reabsorb in the proximal tubules

99
Q

adverse effects of SGLT2 inhibitors

A

increased urination
increased UTIs
hypotension

100
Q

metabolism of SGLT2 inhibitors

A

glucuronidation in the liver and kidneys by uridine diphosphate glucuronosyltransferase-1A9

101
Q

amylin is __________________ with insulin from _______________

A

co-secreted

pancreatic B cell

102
Q

another name for amilyn

A

islet amyloid polypeptide

103
Q

human amylin is unsuitable for ______________ because it ________________

A

pharmacological use

forms amyloid plaques and fibers (potentially toxic)

104
Q

MOA of amylin anaolgs

A

binds to amylin receptor in specific regions of the brain
reduces glucagon release

105
Q

amylin effects

A

inhibits glucagon secretion in alpha cells
appetite suppression
delays gastric emptying
handles both endogenous and exogenous

106
Q

amylin analogs are used for treatment in

A

Type 1 and 2 DM

107
Q

insulin allergy

A

type 1 hypersensitivity
local/systemic urticaria from histamine release by mast cells sensitized by anti-insulin IgE antibodies

108
Q

immune insulin resistance

A

lower titer of circulating IgG anti-insulin antibodies that neutralize the action of insulin
associated with other systemic autoimmune disorders like SLE

109
Q

rapid acting analogs

A

lispro
aspart
glulisine
inhaled insulin

110
Q

short acting insulin

A

human regular

111
Q

intermediate acting insulin

A

human NPH

112
Q

concentrated human regular insulin

A

U500 human regular insulin

113
Q

basal analogs

A

glargine
detemir
degludec

114
Q

premixed products of insulin

A

NPH/regular 70/30
Lispro 50/50
Lispro 75/25
Aspart 70/30

Pharmacology II (5 decks)

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